Cellular and deafness mechanisms underlying connexin mutation-induced hearing loss – A common hereditary deafness

Jeffrey C. Wingard, Hong Bo Zhao

Research output: Contribution to journalReview articlepeer-review

112 Scopus citations

Abstract

Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. However, there is no apparent, demonstrable relationship between specific changes in connexin (channel) functions and the phenotypes of mutation-induced hearing loss. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Cx30 (GJB6), Cx29 (GJC3), Cx31 (GJB3), and Cx43 (GJA1) mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation-induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required.

Original languageEnglish
Article number202
JournalFrontiers in Cellular Neuroscience
Volume9
Issue numberMAY
DOIs
StatePublished - May 29 2015

Bibliographical note

Publisher Copyright:
© 2015 Wingard and Zhao.

Keywords

  • Active cochlear amplification
  • Cochlear development
  • Cochlear supporting cell
  • Gap junction
  • Hair cell
  • Inner ear
  • Non-syndromic hearing loss
  • Potassium recycling

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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